Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival

Sofian Al Shboul*, Olimpia Curran, Javier Antonio Alfaro , Fiona Lickiss, Erisa Nita, Jacek Kowalski, Faris Naji, Rudolf Nenutil, Kathryn L Ball, Radovan Krejcir, Borivoj Vojtesek, Ted R Hupp, Paul Brennan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Better understanding of GBM signalling networks in-vivo would help develop more physiologically relevant ex-vivo models to support therapeutic discovery. A 'func-tional proteomics' screen was undertaken to measure the specific activity of a set of protein kinases in a two-step cell-free biochemical assay to define dominant kinase activities to identify potentially novel drug targets that may have been over-looked in studies interrogating GBM-derived cell lines. A dominant kinase activity derived from the tumour tissue, but not patient-derived GBM stem-like cell lines, was Bruton Tyrosine Kinase (BTK). We demonstrate that BTK is ex-pressed in more than one cell type within GBM tissue; SOX2-positive cells, CD163-positive cells, CD68-positive cells and an unidentified cell population which is SOX2-neg-ative CD163-negative and/or CD68-negative. The data provide a strategy to better mimic GBM tissue ex-vivo by reconstituting more physiologically heterogeneous cell co-culture models including BTK-positive/negative cancer and immune cells. These data also have implications for the design and/or interpretation of emerging clinical trials using BTK inhibitors because BTK expression within GBM tissue was linked to longer patient survival.
Original languageEnglish
JournalLife Science Alliance
Early online date13 Oct 2021
DOIs
Publication statusE-pub ahead of print - 13 Oct 2021

Keywords

  • BTK
  • cell lines
  • GBM
  • Kinomics
  • prognosis
  • cancer stem cell

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